A wide variety of morphology-driven and molecular markers have been studied for their ability to predict disease outcome in prostate cancer. Isaacs et al. (1997) Am. J. Pathol. 150:1511-1521; Koch et al. (2000) J. Urol. 164:749-753; Alers et al. (2000) Lab. Invest. 80:931-942. Traditional morphology driven measures have included tumor grade, volume and pathologic stage. Numerous molecular markers have been proposed for their potential clinical utility including the determination of p21, p27, cyclin D1, p53, bcl-2, E-cadherin, HER-2/neu, matrix metalloproteases, telomerase, GST-π. Isaacs et al. (1997) supra; Koch et al. (2000) supra; Alers et al. (2000) supra; Ross et al. (2002) Exp. Rev. Mol. Diagn. 2:129-142; Stattin et al. (1997) Scand J Urol Nephrol Suppl. 185:1-46. Expanded use of these markers for the individualization of therapy, however, has been hampered by several factors including a lack of universal acceptance of their prognostic significance, problems concerning the specificity and sensitivity of the available testing platforms for each marker, and limited available tissue.
Prostate specific membrane antigen (PSMA) is transmembrane folate hydrolase consisting of 750 amino acids and having a molecular weight of 110 kDa. Israeli et al. (1994) Cancer Res. 54:1807-1811; Murphy et al. (1998) J. Urol. 160:2396-2401; Tasch et al. (2001) Crit. Rev. Immunol 21:249-261. PSMA expression has been consistently demonstrated by immunohistochemistry (IHC) and other techniques in normal and hyperplastic prostate tissues, in prostatic intraepithelial neoplasia (PIN) and in invasive carcinomas. Silver et al. (1997) Clin Cancer Res. 3:81-85; Murphy et al. (1998) Cancer 83:2259-2269; and Bostwick et al. (1998) Cancer 82:2256-2261. PSMA expression and PSMA enzymatic activity are greater in prostate cancer specimens than in benign prostate tissues. Bostwick et al (1998) supra; Lapidus et al. (2000) Prostate 45:350-354. The finding that PSMA is expressed in metastatic prostate cancer has lead to the initial development of diagnostic imaging strategies using anti-PSMA antibodies and subsequently to clinical testing of radio-conjugated anti-PSMA antibodies for the treatment of metastatic disease. Gong et al. (1999) Cancer Metast Rev. 18:483-490; Gong et al. (2000) Mol Urol. 4:217-222; Holmes (2001) Expert Opin Investig Drugs 10:5111-519. The identification of PSMA expression in the neo-vasculature of non-prostate cancers has also encouraged the potential use of anti-PSMA antibody therapies for patients with carcinomas of the kidney, lung, colon, breast and other organs. Liu et al. (1997) Clin Cancer Res 5:2674-2681; Chang et al. (1999) Cancer Res. 59:3192-3198.